The major goal of the proposed project is to delineate the structural development of the human fetal brain both qualitatively and quantitatively with ultra high resolution diffusion tensor imaging (DTI). The structural measurements from DTI will be further correlated to the gene profiles across the fetal cortical plate. Human brain is extraordinarily complex and yet its origin is a simple tubular structure. Its development is characterized by a series of accurately organized events which underlies the mechanisms of dramatic structural changes during fetal development. Revealing detailed anatomy at different stages of human fetal brain development and correlating the anatomical changes to gene profiles aid in understanding not only this highly ordered process, but also the neurobiological foundations of cognitive brain disorders such as mental retardation, autism, schizophrenia, bipolar and language impairment. However, anatomical studies of human brain development during this period are surprisingly scarce and histology-based atlases have become available only recently. Our preliminary data (1-3) and other studies (e.g. 4-9) have supported that DTI is capable of noninvasively delineating the fetal brain structures at both macroscopic and microscopic level. The structural DTI atlas will provide reference standards for diagnostic radiology of premature newborns and a valuable resource to understand the structural development of the entire brain. Factional anisotropy (FA) derived from diffusion tensor and thickness measurements of the subplate provide valuable insights into the cortical maturation. The spatially unique changes of these two measurements are accompanied by the distinctive gene profiles at different locations of the cortical plate. Characterizing the featured structural effects of specific gene expression offers a refreshing window to understand the formation of the brain functions. This study is made possible by collaborating among the three labs: Dr. Huang, Dr. Sestan and Dr. Yarowsky. With gene profiling of the fetal brains (10) from Dr. Sestan's lab, the database incorporating the relationship between the structural changes and gene expression may provide the clues of detecting developmental and cognitive brain disorders at their early stages. In this proposal, we will focus on the development of technologies and databases that will be essential components for this new research field through the following three aims: Aim 1: To establish the two- dimensional (2D) and three-dimensional (3D) digital DTI/MRI atlas of human fetal brain. Aim 2: To delineate the cortical mapping of structural measurement in the cerebral wall. Aim 3: To correlate across the cortical plate the temporal changes of the structural measurements to the quantified gene expression related to developmental functions of synapse formation, axonal growth and myelination.